rs886061312

Variant names:

• chr6-33163142-G-A
• rs886061312
• NM_080680.3:c.*536C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_080680.3(COL11A2):​c.*536C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 152,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: COL11A2 NM_080680.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:4
• Conservation: PhyloP100: 0.410
• Publications: 0 publications found

Genes affected

COL11A2 (HGNC:2187): (collagen type XI alpha 2 chain) This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. It is located on chromosome 6 very close to but separate from the gene for retinoid X receptor beta. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Proteolytic processing of this type XI chain produces PARP, a proline/arginine-rich protein that is an amino terminal domain. Mutations in this gene are associated with type III Stickler syndrome, otospondylomegaepiphyseal dysplasia (OSMED syndrome), Weissenbacher-Zweymuller syndrome, autosomal dominant non-syndromic sensorineural type 13 deafness (DFNA13), and autosomal recessive non-syndromic sensorineural type 53 deafness (DFNB53). Alternative splicing results in multiple transcript variants. A related pseudogene is located nearby on chromosome 6. [provided by RefSeq, Jul 2009]

COL11A2 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 13

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• otospondylomegaepiphyseal dysplasia, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal recessive nonsyndromic hearing loss 53

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• otospondylomegaepiphyseal dysplasia

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• otospondylomegaepiphyseal dysplasia, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• fibrochondrogenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080680.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	NM_080680.3	MANE Select	c.*536C>T		3_prime_UTR	Exon 66 of 66	NP_542411.2	A0A0C4DFS1
	COL11A2	NM_001424108.1		c.*536C>T		3_prime_UTR	Exon 65 of 65	NP_001411037.1
	COL11A2	NM_080681.3		c.*536C>T		3_prime_UTR	Exon 64 of 64	NP_542412.2	Q4VXY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A2	ENST00000341947.7	TSL:5 MANE Select	c.*536C>T		3_prime_UTR	Exon 66 of 66	ENSP00000339915.2	A0A0C4DFS1
	COL11A2	ENST00000930122.1		c.*536C>T		3_prime_UTR	Exon 65 of 65	ENSP00000600181.1
	COL11A2	ENST00000374708.8	TSL:5	c.*536C>T		3_prime_UTR	Exon 64 of 64	ENSP00000363840.4	Q4VXY6

Frequencies

GnomAD3 genomes AF: 0.0000490 AC: 7 AN: 142882 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000251

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000763

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000100 AC: 1 AN: 10004 Hom.: 0 Cov.: 0 AF XY: 0.000189 AC XY: 1 AN XY: 5282

African (AFR) AF: 0.00 AC: 0 AN: 92

American (AMR) AF: 0.00 AC: 0 AN: 1700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 100

East Asian (EAS) AF: 0.00 AC: 0 AN: 438

South Asian (SAS) AF: 0.00 AC: 0 AN: 1152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.000179 AC: 1 AN: 5594

Other (OTH) AF: 0.00 AC: 0 AN: 442

GnomAD4 genome AF: 0.0000490 AC: 7 AN: 142882 Hom.: 0 Cov.: 30 AF XY: 0.0000144 AC XY: 1 AN XY: 69306

African (AFR) AF: 0.0000254 AC: 1 AN: 39320

American (AMR) AF: 0.00 AC: 0 AN: 14390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4218

South Asian (SAS) AF: 0.000251 AC: 1 AN: 3980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000763 AC: 5 AN: 65540

Other (OTH) AF: 0.00 AC: 0 AN: 2006

Alfa AF: 0.0000612 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Fibrochondrogenesis 2 (1)
-	1	-	Otospondylomegaepiphyseal dysplasia, autosomal dominant (1)
-	1	-	Otospondylomegaepiphyseal dysplasia, autosomal recessive (1)
-	1	-	Stickler Syndrome, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.69
PhyloP100		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886061312; hg19: chr6-33130919;